CD109, a negative regulator of TGF-β signaling, is a putative risk marker in diffuse large B-cell lymphoma
CD109, a negative regulator of TGF-β signaling, is a putative risk marker in diffuse large B-cell lymphoma
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DOI：
10.1007/s12185-016-2173-1
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发表时间：
2017-05
影响因子：
2.1
通讯作者：
M. Yokoyama;M. Ichinoe;Sosei Okina;Yasutaka Sakurai;Norihiro Nakada;N. Yanagisawa;Shi‐Xu Jiang;Y. Numata;Atsuko Umezawa;K. Miyazaki;M. Higashihara;Y. Murakumo
中科院分区：
文献类型：
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作者：
M. Yokoyama;M. Ichinoe;Sosei Okina;Yasutaka Sakurai;Norihiro Nakada;N. Yanagisawa;Shi‐Xu Jiang;Y. Numata;Atsuko Umezawa;K. Miyazaki;M. Higashihara;Y. Murakumo
CD109是一种糖基磷脂酰肌醇锚定的糖蛋白，可负调控TGF-β信号。CD109最初是在造血肿瘤中发现的；然而，CD109在造血系统恶性肿瘤中的意义尚不清楚。在这里，我们研究CD109与弥漫性大b细胞淋巴瘤（DLBCL）预后的关系。对84例DLBCL标本进行CD109表达免疫组织化学分析，将31例和53例分别分为CD109低表达组和高表达组。使用Kaplan-Meier分析和log-rank检验，CD109表达与总生存率无相关性（P= 0.17）；然而，高cd109表达与低1年生存率之间存在显著相关性（P= 0.01）。此外，结合修订后的国际预后指数（R-IPI），与单独的R-IPI差相比，R-IPI差/ cd109高与较差的预后相关。我们评估了CD109缺失的Nalm6细胞（一种人b淋巴母细胞白血病/淋巴瘤细胞系）中TGF-β信号传导，发现TGF-β1刺激后Smad2磷酸化比对照细胞延长，表明CD109减弱了人b细胞肿瘤中TGF-β1信号传导。这些结果表明，CD109是鉴别DLBCL患者中高危人群的一种假定的生物标志物。
CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that negatively regulates TGF-β signaling. CD109 was originally identified in hematopoietic tumors; however, the significance of CD109 in hematopoietic malignancies remains unclear. Here, we study the association of CD109 with diffuse large B-cell lymphoma (DLBCL) prognosis. Eighty-four DLBCL specimens were immunohistochemically analyzed for CD109 expression, and 31 and 53 cases were classified into low- and high-CD109 expression groups, respectively. CD109 expression was not associated with overall survival using the Kaplan–Meier analysis and log-rank tests (P= 0.17); however, a significant association was observed between high-CD109 expression and low-1-year survival (P= 0.01). Moreover, in combination with the revised International Prognostic Index (R-IPI), R-IPI-poor/CD109-high was associated with poorer prognosis compared with R-IPI-poor alone. We assessed TGF-β signaling in CD109-depleted Nalm6 cells (a human B-lymphoblastic leukemia/lymphoma cell line), and found prolonged Smad2 phosphorylation compared with control cells after TGF-β1 stimulation, suggesting that CD109 attenuates TGF-β1 signaling in human B-cell tumors. These results suggest that CD109 is a putative biomarker for identifying a high-risk group among DLBCL patients.